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Resistance of chimpanzee T cells to human immunodeficiency virus type 1 Tat-enhanced oxidative stress and apoptosis

CD4+ T-cell depletion in AIDS patients involves induction of apoptosis in human immunodeficiency virus (HIV)-infected and noninfected T cells. The HIV type 1 (HIV-1)-transactivating protein Tat enhances apoptosis and activation-induced cell death (AICD) of human T cells. This effect is mediated by t...

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Main Authors: Ehret, Andreas (Author) , Westendorp, Michael (Author) , Herr, Ingrid (Author) , Debatin, Klaus-Michael (Author) , Heeney, Jonathan L. (Author) , Frank, Rainer (Author) , Krammer, Peter H. (Author)
Format: Article (Journal)
Language:English
Published: September 1, 1996
In: Journal of virology
Year: 1996, Volume: 70, Issue: 9, Pages: 6502-6507
ISSN:1098-5514
DOI:10.1128/jvi.70.9.6502-6507.1996
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1128/jvi.70.9.6502-6507.1996
Verlag, lizenzpflichtig, Volltext: https://journals.asm.org/doi/10.1128/jvi.70.9.6502-6507.1996
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Author Notes:Andreas Ehret, Michael O. Westendorp, Ingrid Herr, Klaus-Michael Debatin, Jonathan L. Heeney, Rainer Frank, Peter H. Krammer
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Summary:CD4+ T-cell depletion in AIDS patients involves induction of apoptosis in human immunodeficiency virus (HIV)-infected and noninfected T cells. The HIV type 1 (HIV-1)-transactivating protein Tat enhances apoptosis and activation-induced cell death (AICD) of human T cells. This effect is mediated by the CD95 (APO-1/Fas) receptor-CD95 ligand (CD95L) system and may be linked to the induction of oxidative stress by Tat. Here we show that HIV-1 Tat-induced oxidative stress is necessary for sensitized AICD in T cells caused by CD95L expression. Tat-enhanced apoptosis and CD95L expression in T cells are inhibited by neutralizing anti-Tat antibodies, antioxidants, and the Tat inhibitor Ro24-7429. Chimpanzees infected with HIV-1 show viral replication resembling early infection in humans but do not show T-cell depletion or progression towards AIDS. The cause for this discrepancy is unknown. Here we show that unlike Tat-treated T cells in humans, Tat-treated chimpanzee T cells do not show downregulation of manganese superoxide dismutase or signs of oxidative stress. Chimpanzee T cells are also resistant to Tat-enhanced apoptosis, AICD, and CD95L upregulation.
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Physical Description:Online Resource
ISSN:1098-5514
DOI:10.1128/jvi.70.9.6502-6507.1996

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